Sanchez-Quintero, Maria JTorres, Maria JBlazquez, Ana BGómez, EnriqueFernandez, Tahia DDoña, InmaculadaAriza, AdrianaAndreu, InmaculadaMelendez, LidiaBlanca, MiguelMayorga, Cristobalina2013-11-142013-11-142013-09-16Sanchez-Quintero MJ, Torres MJ, Blazquez AB, Gómez E, Fernandez TD, Doña I, et al. Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients. PLoS ONE. 2013; 8(9):e74198http://hdl.handle.net/10668/1377Journal Article;Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.enAmoxicilinaCélulas dendríticasLigandosSinergismo medicamentosoHipersensibilidad retardadaLinfocitosCitocinasExantemaHumanosMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::AmoxicillinMedical Subject Headings::Anatomy::Cells::Antigen-Presenting Cells::Dendritic CellsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::LigandsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug Interactions::Drug SynergismMedical Subject Headings::Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, DelayedMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::LymphocytesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::CytokinesMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Skin Diseases::ExanthemaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humansresearch article24066120open access10.1371/journal.pone.00741981932-6203PMC3774803